What is the immediate treatment for a patient diagnosed with Thrombotic Thrombocytopenic Purpura (TTP)?

Immediate Treatment for Thrombotic Thrombocytopenic Purpura (TTP)

Immediately initiate therapeutic plasma exchange (PEX) combined with corticosteroids and immunosuppressive therapy as soon as TTP is suspected—delay in treatment is associated with increased mortality. 1

Critical First Steps

The moment TTP is suspected based on thrombocytopenia and microangiopathic hemolytic anemia, treatment must begin emergently:

• Obtain immediate hematology consultation 1
• Stabilize the patient and address any critical organ dysfunction 1
• Do NOT wait for ADAMTS13 results to initiate treatment—the diagnosis is clinical, and therapy must start immediately 2, 3

Core Treatment Regimen

Therapeutic Plasma Exchange (PEX)

• Perform daily PEX at 1-1.5 times plasma volume using fresh frozen plasma (FFP) as replacement fluid 2
• Continue daily PEX until platelet count normalizes (>150,000/µL) and LDH normalizes, then slowly taper 2
• PEX is the cornerstone of therapy and has transformed survival from near zero to approximately 93% 4

Corticosteroids

• Administer methylprednisolone 1 g IV daily for 3 days, with the first dose given immediately after the first PEX 1
• Alternatively, prednisone 1-2 mg/kg/day can be used 1

Immunosuppression with Rituximab

• Initiate rituximab 375 mg/m² weekly for 4 doses concurrently with PEX and corticosteroids 1, 4
• This combination improves survival to approximately 93% 4

Adjunctive Therapy: Caplacizumab

Consider adding caplacizumab, particularly for severe cases or when ADAMTS13 activity is suppressed with inhibitor present 1, 5:

• Give 11 mg IV bolus before the first PEX, then 11 mg subcutaneously daily after each PEX session 5
• Continue for the duration of daily PEX plus 30 days thereafter 5
• If ADAMTS13 activity remains suppressed after initial treatment, extend caplacizumab for 7-day intervals up to maximum 28 additional days 5

Benefits and Risks of Caplacizumab

• Reduces time to platelet normalization and decreases early recurrence risk by 29% 4
• Warning: Increases bleeding risk by 17%—monitor closely for excessive bleeding 4, 5
• Particularly valuable when ADAMTS13 activity is <10% with elevated anti-ADAMTS13 IgG 1

Essential Diagnostic Workup (Perform Concurrently, Not Before Treatment)

While initiating treatment, obtain:

• Peripheral blood smear to confirm schistocytes 1
• ADAMTS13 activity level and inhibitor titer 1
• LDH, haptoglobin, reticulocyte count, bilirubin 1
• Coagulation studies (PT, aPTT, fibrinogen) 1
• Blood type and antibody screen, direct antiglobulin test 1
• Imaging based on symptoms (CT/MRI brain for neurologic symptoms, echocardiogram for cardiac involvement) 1

Critical Pitfalls to Avoid

• Never delay PEX while waiting for ADAMTS13 results—thrombocytopenia plus microangiopathic hemolytic anemia is sufficient to start treatment 2, 3
• Do NOT transfuse platelets unless life-threatening bleeding occurs—platelet transfusion can worsen thrombosis 1
• If RBC transfusion is needed, transfuse only the minimum necessary to relieve symptoms or reach hemoglobin 7-8 g/dL 1
• Avoid heparin-based anticoagulants due to potential cross-reactivity with heparin-induced thrombocytopenia 1

Monitoring During Treatment

• Continue daily PEX until platelet count >150,000/µL and LDH normalizes 2
• Monitor for signs of persistent disease (suppressed ADAMTS13 activity <10%) 5
• If no improvement or worsening on corticosteroids, add additional immunosuppression (cyclosporine, IVIG, MMF, or ATG) 1
• After stopping caplacizumab, monitor closely for relapse—patients with ADAMTS13 <10% at treatment end are at high risk 5

Special Considerations for Severe Cases

For life-threatening complications (CNS hemorrhage/thrombosis, renal failure):

• Admit to ICU for close monitoring and rapid life-sustaining interventions 6
• Consider emergency splenectomy if refractory to medical therapy 1
• For surgical interventions with low platelets/fibrinogen, give platelet transfusion or fibrinogen replacement only perioperatively 1